The metabolism of the corticosteroid side-chain is being studied in man and animals. This is accomplished by utilizing corticosteroids labelled with tritium at position 21 and 14C at position 4 ((4-14C-21-3H)-corticosteroids). The objectives are to determine the significance of a pathway of degradation which leads to the formation of steroidal carboxylic acids and loss of tritium of the methylol group. The steroidal 20-hydroxyl-21-oic acids derived from cortisol, named the cortoic acids, are excreted into the urine. The enzyme, 20-hydroxy acid synthetase, catalyzes the formation of the cortoic acids. Other enzymes, the ketoaldehyde dehydrogenases, catalyze synthesis of steroidal 20-keto acids. The metabolic role of a new class of steroid, the "isocorticosteroids" containing the 17-aldol side chain which we believe to be intermediate in the synthesis of 21-oic acids, is under study. Simple analytical procedures for the quantitative measurement of steroidal carboxylic acids are under development for clinical application.